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It is thought that the Charrúa were driven south into present-day Uruguay by the Guaraní people around 4000 years ago.[4]

A legend said the Charrúa killed Spanish explorer Juan Díaz de Solís during his 1515 voyage up the Río de la Plata, but was contradicted by researchers who said that this people was not cannibalistic and that it was actually the Guaranis who did it. Later on, it was proven that they were no direct testimony of this moment. Following the arrival of European settlers, the Charrúa, along with the Chana, strongly resisted their territorial invasion. In the 18th and 19th centuries the Charruas were confronted to cattle exploitation that strongly altered their way of life which caused famine and forced them to rely on cows and sheeps. Unfortunately, those were in that epocha increasingly privatized. Malones (raids) were resisted by settlers who freely shooted any indigenous people on their way. Later on, Fructuoso Rivera - Uruguay's first president - who possessed an hacienda organized the Charruas's genocide. Since 11 April 1831, when the Salsipuedes (meaning "Get-out-if-you-can") campaign was launched by a group led by Bernabé Rivera, nephew of Fructuoso Rivera, it is said that the Charruas were extinct.

Four surviving Charrúas were captured at Salsipuedes. They were Senacua Sénaqué, a medicine man; Vaimaca-Pirú Sira, a warrior; and a young couple, Laureano Tacuavé Martínez and María Micaëla Guyunusa. All four were taken to Paris, France, in 1833, where they were exhibited to the public. They all soon died in France, including a baby daughter born to Sira and Guyunusa, and adopted by Tacuavé.[2] The child was named María Mónica Micaëla Igualdad Libertad by the Charrúas, yet she was filed by the French as Caroliné Tacouavé.[5][6] A monumental sculpture, Los Últimos Charrúas was built in their memory in Montevideo, Uruguay.[7]

Since the 80's - after Uruguay's last dictatorship -, a group of people is affirming and revendicating their Charruan ancestry.

Not much is known about the Charrúa due to their cognitive erasure at an early time in the Uruguayan history. The only surviving documents that concern the Charrúas were those of Spanish explorers, archaeologists and anthropologists. A new literature is now emergence about their ethnogenesis and activism.

Uruguayans refer to themselves as "charrúas" when in the context of a competition or battle against a foreign contingent. In situations in which Uruguayans display bravery in the face of overwhelming odds, the expression "garra charrúa" (Charrúan tenacity) is used to refer to victory in the face of certain defeat.

After Salsipuedes, the Charrúa effectively ceased to exist as a nation. It is believed that there are no full-blooded Charrúa remaining, though physical and genetic traces are found amongst Uruguay's population. According to the Argentine census of 2001, there are 676 Charrúa (the majority of whom are of mixed ancestry) living in the province of Entre Ríos.